Abstract

Abstract Introduction Low-intensity extracorporeal shockwave therapy (LiESWT) is thought to treat erectile dysfunction (ED) but the mechanism remains elusive. It is believed that LiESWT may work by stimulating neovascularization and nerve regeneration as demonstrated in animal models by histologically increased angiogenesis-related growth factors and neuronal factors including vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS) and brain derived-neurotropic factor (BDNF). Given its prolific use, a thorough understanding of the mechanism of action of this therapy at a cellular level is critical prior to recommendation of this therapy on a larger scale. Objective Objective data post LiESWT is sparse. In this study, we aimed to determine whether markers for neovascularization and nerve regeneration can be detected in the serum of penile tissue in men following LiESWT treatment. We hypothesized that LiESWT results in appreciable increases in vascular and neuronal factors post therapy. Methods Patients were prospectively enrolled in a clinical trial of LiESWT for ED. Patients received 12 bi-weekly LiESWT treatments of 0.2mJ/mm2 at 5Hz, 1500 shocks delivered per treatment, with follow up at 1-2 weeks, 4-6 weeks, 3 months and 6 months post-treatment. Cavernosal penile blood samples were obtained prior to treatment and at each visit post-treatment. The concentrations of eNOS, nNOS, VEGF, and BDNF in penile plasma samples were measured using Enzyme-Linked Immunosorbent Assay (ELISA) with specific commercial kits, following the protocols provided by the manufacturer. Results Twenty-five patients completed all five study visits. Mean patient age was 63. Mean baseline IIEF-EF score prior to treatment was 14.24 (±1.21). At the time of data analysis, plasma samples from 9 men were analyzed for BDNF, eNOS, and nNOS levels using the ELISA assay, and samples from all 25 men were analyzed for VEGF. BDNF levels demonstrated a sustained decrease after the first treatment (P = 0.0001, Figure 1A). Levels of eNOS were noted to trend upward, but no significant changes in eNOS, nNOS or VEGF levels were noted. Conclusions To our knowledge, this is the first study in human tissues to attempt to quantify objective measures of neurogenesis and neovascularization in penile tissue following LiESWT for ED. Though our N is small, our results suggest that LiESWT may decrease BDNF levels after initial LiESWT treatment while VEGF, eNOS and nNOS levels remain unchanged. The clinical significance of these findings is currently unknown, as our findings are not consistent with histological studies in animals which demonstrate upregulation of these markers in penile tissues. However, we believe this represents a promising first step in attempting to understand the effect of LiESWT at a tissue level in men undergoing LiESWT. Disclosure No.

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